title: Production of free glutamate in milk requires the leucine transporter LAT1.
abstract: The concentration of free glutamate (Glu) in rat's milk is ∼10 times higher than that in plasma. Previous work has shown that mammary tissue actively transports circulatory leucine (Leu), which is transaminated to synthesize other amino acids such as Glu and aspartate (Asp). To investigate the molecular basis of Leu transport and its conversion into Glu in the mammary gland, we characterized the expression of Leu transporters and [(3)H]Leu uptake in rat mammary cells. Gene expression analysis indicated that mammary cells express two Leu transporters, LAT1 and LAT2, with LAT1 being more abundant than LAT2. This transport system is sodium independent and transports large neutral amino acids. The Leu transport system in isolated rat mammary cells could be specifically blocked by the LAT1 inhibitors 2-aminobicyclo-[2.2.1]-heptane-2-carboxylic acid (BCH) and triiodothyronine (T3). In organ cultures, Glu secretion was markedly inhibited by these LAT1 inhibitors. Furthermore, the profiles of Leu uptake inhibition by amino acids in mammary cells were similar to those reported for LAT1. In vivo, concentrations of free Glu and Asp increased in milk by oral gavage with Leu at 6, 12, and 18 days of lactation. These results indicate that the main Leu transporter in mammary tissue is LAT1 and the transport of Leu is a limiting factor for the synthesis and release of Glu and Asp into milk. Our studies provide the bases for the molecular mechanism of Leu transport in mammary tissue by LAT1 and its active role on free Glu secretion in milk, which confer umami taste in suckling pups.
authors.affiliation: Frontier Research Laboratories, Institute for Innovation, Ajinomoto Corporation, Kawasaki-ku, Kawasaki-shi, Japan; and.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakamura
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Nakamura
authors.forename: Mariko
authors.initials: M
authors.lastname: Hirota
authors.forename: Ana
authors.initials: A
authors.lastname: San Gabriel
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Nattida
authors.initials: N
authors.lastname: Chotechuang
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Uneyama
authors.forename: Kunio
authors.initials: K
authors.lastname: Torii
mesh_terms: D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000378:metabolism; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D005260:Female; D027301:Fusion Regulatory Protein 1, Light Chains / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics / Q000378:metabolism*; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism; D008892:Milk / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D027182:Amino Acid Transport System y+; D000596:Amino Acids; D027301:Fusion Regulatory Protein 1, Light Chains; D027283:Large Neutral Amino Acid-Transporter 1; C486582:Slc7a8 protein, rat; D018698:Glutamic Acid; D007930:Leucine
keywords: BCAA; amino acid; amino acid transporters; glutamate; lactation; leucine; mammary tissue; milk; umami taste